rs916943

Positions:

• chr7-15554143-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004320.2(AGMO):​c.257+5998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,090 control chromosomes in the GnomAD database, including 635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.087 (635 hom., cov: 31)
• Consequence: AGMO NM_001004320.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

AGMO (HGNC:33784): (alkylglycerol monooxygenase) The protein encoded by this gene is a tetrahydrobiopterin- and iron-dependent enzyme that cleaves the ether bond of alkylglycerols. Sequence comparisons distinguish this protein as forming a third, distinct class of tetrahydrobiopterin-dependent enzymes. Variations in this gene have been associated with decreased glucose-stimulated insulin response, type 2 diabetes, and susceptibility to intracranial aneurysms. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGMO	NM_001004320.2	c.257+5998G>A		intron_variant		ENST00000342526.8	NP_001004320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGMO	ENST00000342526.8	c.257+5998G>A		intron_variant		1	NM_001004320.2	ENSP00000341662	P1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13232 AN: 151972 Hom.: 634 Cov.: 31

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0871 AC: 13250 AN: 152090 Hom.: 635 Cov.: 31 AF XY: 0.0868 AC XY: 6455 AN XY: 74346

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.103 Hom.: 1177

Bravo AF: 0.0799

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs916943; hg19: chr7-15593768;